This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Blood platelets are small (3 micron diameter and &lt;1 micron thick) cellular fragments generated from macrophages. They circulate in the bloodstream and play a major role in primary hemostasis. Some platelet defects can lead to an array of bleeding disorders, while others can significantly increase risk for thrombotic events such as pulmonary embolism, heart attack and stroke. Platelets naturally lack nuclei, rendering them much thinner than typical eukaryotic cells, yet they still contain mitochondria, microtubules, an actin cytoskeleton and other eukaryotic features. They also contain other structures unique to their role. Thus they are an excellent target for structural analysis by electron cryotomography. Our goals are 1) to describe the cellular structures of platelets in 3D;the cytoskeleton, including actin and microtubules;the membrane systems, both plasma and intracellular;other organelles such as mitochondria;and macromolecular machines such as ribosomes, etc.;and finally their relationships to each other. 2) All these structures and relationships change upon activation by a clotting signal. We can observe the progression of events by setting up a time course of activation.